Worldwide incidence of cutaneous leishmaniasis averages approximately 1.25 million cases per annum. In the Americas, the formerly dominant sylvatic cycle of transmission has become secondary to an emerging domestic transmission cycle within the past decade. Very recently, several outbreaks of American Cutaneous Leishmaniasis (ACL) have occurred (1,000-2,000 cases each) in rural districts with low endemicity (<50 cases per annum). The availability of state and local surveillance resources, along and the availability of adjacent non-endemic districts to serve as control sites, has provided a unique opportunity to determine factors leading to (a) the epidemic establishment and (b) the domesticity of the transmission cycle. The project developed herein focuses on a district involved in an epidemic of >2,000 cases across 112 townships and has evolved the following specific aims: (1) To detect a human-to-sand fly-to-human mode of transmission. The normal sylvatic mode of transmission to humans is via a reservoir animal to sand fly. (2) To determine the roles of the common peridomestic animals?opossums, dogs and equines?as parasite reservoirs. (3) To incriminate the insect vector species. Four species are identified in the epidemic areas, but details of their density, vector competence and host preference are not characterized. (4) To examine the population genetic structure of a newly dominant vector species, Lutzomyia longiflocosa, for its genetic heterogeneity and ecological origins. (5) To model vector-reservoir-human relationships for optimization of control strategies. State of art field methods and analytic tools will be employed, including molecular genetic strategies (gene sequencing, SSCP gel sieving), geographical information systems (including local mapping with GPS and remotely sensed imagery), and iterative modeling.